Key Molecular Step to Fighting Off Viruses Identified

UT Southwestern Medical Center researchers have determined how a protein
that normally latches onto molecules inside cells and marks them for
destruction also gives life to the body's immune response against
viruses.

The researchers discovered that a certain form of the "death" protein
ubiquitin interacts with another protein, called RIG-I, but does not
mark it for destruction. Instead, this form of ubiquitin binds to and
activates RIG-I, which is known to trigger the body's immune system when
a virus invades a cell.

Dr. Zhijian "James" Chen, professor of molecular biology at UT
Southwestern, is senior author of the study, which is available online
and in the journal Cell.

Dr. Chen and his colleagues reconstituted key elements of the human
innate immune system in laboratory test tubes and found ubiquitin forms a
unique chain-like structure that associates with RIG-I before RIG-I can
get to work fighting viruses. The innate immune system is the body's
first generic response against invading pathogens.

"Activation of RIG-I is the first line of our immune defenses against
viral infections," said Dr. Chen, an investigator for the Howard Hughes
Medical Institute at UT Southwestern. "Understanding how it comes to
life is a key step in developing new approaches to antiviral therapies.
Having this test-tube system could help us identify substances that
enhance the body's antiviral immunity."

Dr. Chen said his team's experiments mark the first time innate
immunity has been recapitulated in a test tube. The findings provide one
of the missing pieces in the complex puzzle of how the body fights off
infection, he added.

Dr. Chen is now focusing on how activated RIG-I interacts with
another protein called MAVS, also essential for immune response.